eISSN: 2084-9869
ISSN: 1233-9687
Polish Journal of Pathology
Current issue Archive Manuscripts accepted About the journal Supplements Abstracting and indexing Subscription Contact Instructions for authors
SCImago Journal & Country Rank
vol. 69
Original paper

Peritoneal fluid stimulates neoplastic transformation of normal HEK 293 cells by high expression of pluripotent genes

Ilona Szabłowska-Gadomska, Magdalena Ducher, Magdalena Orzechowska, Joanna Bogusławska-Duch, Magdalena Kowalska, Helena Poławska, Maciej Małecki

Pol J Pathol 2018; 69 (3): 299-310
Online publish date: 2018/11/20
View full text
Get citation
JabRef, Mendeley
Papers, Reference Manager, RefWorks, Zotero
Gynecological cancers constitute a serious problem in the world. Their advanced stages are often characterized by the accumulation of ascites, which leads to spreading of cancer cells outside their primary focus. Despite progress in the treatment, prognoses are still not satisfactory. The main causes of these failures are chemoresistance, metastases and recurrences of the disease, which is influenced by, among others, the microenvironment of cancer cells. This study investigated the effect of the microenvironment, which create ascites derived from patients with ovarian and endometrial cancer to non-gynecological HEK 293 cells. The effect of the gynecological cancer microenvironment on HEK 293 cells behaviour was analysed using RT-PCR, qRT-PCR, Western blotting and functional analysis (invasion assays, hanging drop) methods. Our results suggest that the key genes for the development of cancer can be regulated by epigenetic and hypoxia-inducible factor in dependent manner. It was observed that in vitro microenvironment, which is created by cells originating from patients with gynecological cancer (ovarian cancer, endometrial cancer) is able to generate changes in HEK 293 cells by itself.

microenvironment, ascites, ovarian cancer, endometrial cancer, pluripotency

Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer 2013; 49: 1374-1403.
Matte I, Lane D, Bachvarov D, et al. Role of malignant ascites on human mesothelial cells and their gene expression profiles. BMC Cancer 2014; 14: 288.
Gerhauser C. Cancer chemoprevention and nutriepigenetics: state of the art and future challenges. Top Curr Chem 2013; 329: 73-132.
Yoshihara K, Tajima A, Komata D, et al. Gene expression profiling of advanced-stage serous ovarian cancers distinguishes novel subclasses and implicates ZEB2 in tumor progression and prognosis. Cancer Sci 2009; 100: 1421-1428.
Puiffe ML, Le Page C, Filali-Mouhim A, et al. Characterization of ovarian cancer ascites on cell invasion, proliferation, spheroid formation, and gene expression in an in vitro model of epithelial ovarian cancer. Neoplasia 2007; 9: 820-829.
Ahmed N, Riley C, Oliva K, et al. Ascites induces modulation of alpha6beta1 integrin and urokinase plasminogen activator receptor expression and associated functions in ovarian carcinoma. Br J Cancer 2005; 92: 1475-1485.
Herceg Z, Vaissière T. Epigenetic mechanisms and cancer: an interface between the environment and the genome. Epigenetics 2011; 6: 804-819.
Grønbaek K, Hother C, Jones PA. Epigenetic changes in cancer. APMIS 2007; 115: 1039-1059.
Bird AP, Wolffe AP. Methylation-induced repression – belts, braces, and chromatin. Cell 1999; 99: 451-454.
Murphy SK. Targeting the epigenome in ovarian cancer. Future Oncol 2012; 8: 151-164.
Chambers I, Tomlinson SR. The transcriptional foundation of pluripotency. Development 2009; 136: 2311-2322.
Shi W, Wang H, Pan G, et al. Regulation of the pluripotency marker Rex-1 by Nanog and Sox2. J Biol Chem 2006; 281: 23319-23325.
Takahashi K, Tanabe K, Ohnuki M, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007; 131: 861-872.
Zhang X, Cruz FD, Terry M, et al. Terminal differentiation and loss of tumorigenicity of human cancers via pluripotency-based reprogramming. Oncogene 2013; 32: 2249-2260.
Peng S, Maihle NJ, Huang Y. Pluripotency factors Lin28 and Oct4 identify a sub-population of stem cell-like cells in ovarian cancer. Oncogene 2010; 29: 2153-2159.
Zhang Z, Zhu Y, Lai Y, et al. Follicle-stimulating hormone inhibits apoptosis in ovarian cancer cells by regulating the OCT4 stem cell signaling pathway. Int J Oncol 2013; 43: 1194-1204.
Haan C, Behrmann I. A cost effective non-commercial ECL-solution for Western blot detections yielding strong signals and low background. J Immunol Methods 2007; 318: 11-19.
Gardner MJ, Jones LM, Catterall JB, et al. Expression of cell adhesion molecules on ovarian tumour cell lines and mesothelial cells, in relation to ovarian cancer metastasis. Cancer Lett 1995; 91: 229-234.
Flate E, Stalvey JR. Motility of select ovarian cancer cell lines: effect of extra-cellular matrix proteins and the involvement of PAK2. Int J Oncol 2014; 45: 1401-1411.
Kramer N, Walzl A, Unger C, et al. In vitro cell migration and invasion assays. Mutat Res 2013; 752: 10-24.
Yamaguchi H, Wyckoff J, Condeelis J. Cell migration in tumors. Curr Opin Cell Biol 2005; 17: 559-564.
Gawrychowski K, Szewczyk G, Skopiñska-Ró¿ewska E, et al. The angiogenic activity of ascites in the course of ovarian cancer as a marker of disease progression. Dis Markers 2014; 2014: 683757.
Sodek KL, Ringuette MJ, Brown TJ. Compact spheroid formation by ovarian cancer cells is associated with contractile behavior and an invasive phenotype. Int J Cancer 2009; 124: 2060-2070.
Lin RZ, Chang HY. Recent advances in three-dimensional multicellular spheroid culture for biomedical research. Biotechnol J 2008; 3: 1172-1184.
Soncin S, Lo Cicero V, Astori G, et al. A practical approach for the validation of sterility, endotoxin and potency testing of bone marrow mononucleated cells used in cardiac regeneration in compliance with good manufacturing practice. J Transl Med 2009; 7: 78.
Nieborowska-Skorska M, Hoser G, Rink L, et al. Id1 transcription inhibitor- matrix metalloproteinase 9 axis enhances invasiveness of the breakpoint cluster region/abelson tyrosine kinase-transformed leukemia cells. Cancer Res 2006; 66: 4108-4116.
Berx G, van Roy F. Involvement of members of the cadherin superfamily in cancer. Cold Spring Harb Perspec Biol 2009; 1: a003129.
Sawada K, Mitra AK, Radjabi AR, et al. Loss of E-Cadherin promotes ovarian cancer metastasis via alpha 5-integrin, which is a therapeutic target. Cancer Res 2008; 68: 2329-2339.
Lau MT, Klausen C, Leung PC. E-cadherin inhibits tumor cell growth by suppressing PI3K/Akt signaling via β-catenin-Egr1-mediated PTEN expression. Oncogene 2011; 30: 2753-2766.
Dong LL, Liu L, Ma CH, et al. E- cadherin promotes proliferation of human ovarian cancer cells in vitro via activating MEK/ERK pathway. Acta Pharmacol Sin 2012; 33: 817-822.
Daraï E, Scoazec JY, Walker-Combrouze F, et al. Expression of cadherins in benign, borderline, and malignant ovarian epithelial tumors: a clinicopathologic study of 60 cases. Hum Pathol 1997; 28: 922-928.
Forristal CE, Wright KL, Hanley NA, et al. Hypoxia inducible factors regulate pluripotency and proliferation in human embryonic stem cells cultured at reduced oxygen tensions. Reproduction 2010; 139: 85-97.
Jing SW, Wang YD, Chen LQ, et al. Hypoxia suppresses E-cadherin and enhances matrix metalloproteinase-2 expression favoring esophageal carcinoma migration and invasion via hypoxia inducible factor-1 alpha activation. Dis Esophagus 2013; 26: 75-83.
Adamaki M, Georgountzou A, Moschovi M. Cancer and the cellular response to hypoxia. Pediatr Therapeut 2012; Suppl 1: S1.
Keith B, Simon MC. Hypoxia- inducible factors, stem cells, and cancer. Cell 2007; 129: 465-472.
Kelly RD, Cowley SM. The physiological roles of histone deacetylase (HDAC) 1 and 2: complex co-stars with multiple leading parts. Biochem Soc Trans 2013; 41: 741-749.
Dovey OM, Foster CT, Cowley SM. Histone deacetylase 1 (HDAC1), but not HDAC2, controls embryonic stem cell differentiation. Proc Natl Acad Sci USA 2010; 107: 8242- 8247.
Jin KL, Pak JH, Park JY, et al. Expression profile of histone deacetylases 1, 2 and 3 in ovarian cancer tissues. J Gynecol Oncol 2008; 19: 185-190.
Hayashi A, Horiuchi A, Kikuchi N, et al. Type- specific roles of histone deacetylase (HDAC) overexpression in ovarian carcinoma: HDAC1 enhances cell proliferation and HDAC3 stimulates cell migration with downregulation of E- cadherin. Int J Cancer 2010; 127: 1332-1346.
Peinado H, Ballestar E, Esteller M, et al. Snail mediates E-cadherin repression by the recruitment of the Sin3A/ histone deacetylase 1(HDAC1)/HDAC2 complex. Mol Cell Biol 2004; 24: 306-319.
Quick links
© 2018 Termedia Sp. z o.o. All rights reserved.
Developed by Bentus.
PayU - płatności internetowe